crossing96/oncoscreening huggingface dataset:
High-grade neuroendocrine carcinoma of the urachus-report of 3 cases.	Most urachal malignancies are composed of pure adenocarcinoma with mucin production. Urachal neuroendocrine carcinoma (NEC) is extremely rare, with only a few cases reported in the literature. Here we report 3 cases of urachal NEC, the largest series of this rare disease from a single institution. The patients were young, with a mean age of 27 years (range, 23-34). The urachal tumors showed 2 distinct components: high-grade NEC and enteric-type adenocarcinoma. The urachal NECs were composed of small cell carcinoma (n=2) or large cell NEC (n=1). The subsequent resection specimens showed that all the tumors were at advanced Sheldon stages. All 3 patients developed metastases, which were composed of NEC exclusively. Two patients died from disease in 10 and 31 months, respectively, and the third patient was alive with widespread metastases at 21 months. Our findings suggest that urachal NEC is an aggressive variant with an overwhelming growth advantage over conventional adenocarcinoma. The presence of high-grade NEC in the urachus is associated with poor prognosis.	bladder
EpCAM Expression in Lymph Node Metastases of Urothelial Cell Carcinoma of the Bladder: A Pilot Study.	In this retrospective pilot study, the feasibility of the epithelial cell adhesion molecule (EpCAM) as an imaging target for lymph node (LN) metastatic disease of urothelial cell carcinoma (UCC) of the bladder was investigated. LN metastases and LNs without metastases of patients who underwent pelvic lymph node dissection because of muscle invasive bladder cancer (MIBC) were used. Primary tumors of the same patients were used from cystectomy specimen, transurethral resections, and biopsies. A pathologist, blinded to clinical data, scored EpCAM immunoreactivity. This method determines a total immunostaining score, which is the product of a proportion score and an intensity score. EpCAM expression was observed in 19/20 (95%) LNs with UCC metastases and in 11/12 (92%) of the primary tumors. EpCAM expression was absent in 14/14 (100%) LNs without metastases. Median EpCAM expression (TIS) in LN metastases was 5 (IQR 2.0-8.0) and in the primary tumors 6 (IQR 2.3-11.0). Based on the absence of staining in LNs without metastases, EpCAM show high tumor distinctiveness. EpCAM seems to be a feasible imaging target in LN metastases of UCC of the bladder. Pre- and perioperative visualization of these metastases will improve disease staging and improve the complete resection of LN metastases in MIBC.	bladder
Predicting Grade and Stage at Cystoscopy in Newly Presenting Bladder Cancers-a Prospective Double-Blind Clinical Study.	OBJECTIVE: To assess urologists' ability to predict the grade and stage of new bladder cancers from the cystoscopic features alone. PATIENTS AND METHODS: We conducted a prospective clinical study on consecutive patients who underwent transurethral resection of bladder tumor (TURBT) for new bladder cancers. Using only cystoscopic tumor morphology at the time of initial TURBT, 3 urology consultants predicted the grade and stage, recording these on a proforma along with tumor features. Predictions were compared with assessments by uropathologists, blinded to the clinical prediction. We analyzed the accuracy in (1) predicting the exact grade and stage of the cancer; (2) differentiating between low- and high-grade cancers; and (3) discerning between Ta, T1, and T2 cancers. RESULTS: Of 248 patients, 224 were suitable for analysis. The positive predictive values for low- and high-grade cancers were 85.8% and 71.3%, respectively. The overall likelihood of a consultant predicting high-grade cancers as being low grade was 16/83 (19.3%). When tumors were large (>30 mm), this likelihood dropped significantly to 7.3% (4/55) (odds ratio = 3.1, 95% confidence interval = 1.0-9.7, P = .04). Non-muscle-invasive and muscle-invasive cancers were predicted accurately in 93.4% and 85.2% patients, respectively. Six of 161 (3.7%) tumors predicted to be non-muscle-invasive bladder cancer were actually muscle invasive on histology. CONCLUSION: For clinical purposes, in newly presenting patients with bladder cancer, urologists appear to reliably predict lower grade and muscle-invasive disease, confirming widely held belief. This allows for appropriate and efficient use of surgical expertise, available technology, and selection of participants for clinical trials on the basis of prehistology risk categories.	bladder
The anti-tumor effect of intravesical administration of normal urothelial cells on bladder cancer.	BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need. Like other cancers, UBC to the host body is considered as a wound, aging stem cell disease and immunosuppressive disorder. Therefore, we proposed a novel cellular approach to target the host body by intravesical instilling of normal urothelial cells that could repair the injury and reduce inflammation by activating body-reparative capacity and because non-self cells are transplanted, host body immune responses could be induced in the tumor microenvironment of UBC to restrain and even eliminate tumor cells. METHODS: In this study, we isolated and expanded normal male murine urothelial cells and intravesically administered them into the bladders of female mice of two orthotopic bladder tumor models and one urothelial injury model. RESULTS: We showed that the instillation of normal urothelial cells containing stem/progenitor cell population into bladders could have anti-tumor effect in orthotopic tumor models, possibly by activating immune responses and helping injured urothelium tissue recovery in a chemically induced urothelial injury model. CONCLUSIONS: Our findings could lead to an innovative and revolutionary cell therapy modality with normal urothelial cells as an effective and safe therapeutic option for UBC.	bladder
[Clinical value of fluorescence in situ hybridization positive of exfoliated urothelial cells in urothelial carcinoma].	OBJECTIVE: To analyze the clinical pathologic characteristics of cases with fluorescence in situ hybridization (FISH) positive of exfoliated urothelial cells, so as to evaluate the clinical utility of FISH in the diagnosis of urothelial carcinoma (UC). METHODS: A total of 271 cases of FISH positive in Department of Urology of Peking University First Hospital from Apr. 2012 to Sep. 2015 were recruited in this study. Retrospective analysis was made on their clinical data. For FISH analysis, labeled probes specific for chromosomes 3, 7, 17, and the p16 (9p21) gene were used to assess chromosomal abnormalities indicative of malignancy. The positive predict values (PPV) of all the techniques were analyzed. RESULTS: Of the 271 patients, 207 cases were UC, 7 cases were non-UC, and 57 cases were benign diseases. The PPV of FISH in detecting UC was 76.4%, while the 95% confidence interval (CI) 71.3% to 81.5%. In the cohort of FISH positive, this value was similar to that of urinary cytology (PPV 86.8%, 95% CI: 78.5%-95.0%). The PPV of FISH was lower than that of cystoscopy and ureteroscopy (PPV 96.1%, 95% CI: 91.7%-100.0%). There were significant differences between this study and the PPV of FISH reported abroad (PPV 53.9%, χ(2)=33.048, P<0.001). Of all the UC with FISH positive, bladder cancer showed an earlier pathological stage versus renal pelvic carcinoma and ureteral carcinoma, with significance (χ(2)=5.894, P=0.015, and χ(2)=13.601, P<0.001, respectively). However, no difference was found in the size, pathological stage and pathological grade of tumors between the urinary cytology positive group and the urinary cytology negative group. The rate of high-grade UC in ureteral carcinoma of FISH positive was 92.3%, much higher than that of ureteral carcinoma reported domestically. CONCLUSION: The PPV of FISH in detecting UC is higher relatively, with a better clinic value for Chinese patients. The ureteral carcinoma with FISH positive obtains a higher pathological grade, which is of great guiding significance for UC.	bladder
Intravoxel incoherent motion diffusion-weighted imaging in assessing bladder cancer invasiveness and cell proliferation.	BACKGROUND: Nonmuscle-invasive bladder cancer (NMIBC, Stage T1 or lower) is treated with transurethral resection (TUR), while muscle-invasive bladder cancer (MIBC, Stage T2 or more) requires neoadjuvant chemotherapy before radical cystectomy. Hence, preoperative differentiation is vital. PURPOSE: To investigate whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can differentiate NMIBC from MIBC and to assess whether there were correlations between IVIM parameters and the Ki-67 labeling index (LI). STUDY TYPE: Retrospective. SUBJECTS: Thirty-six patients diagnosed with bladder cancer confirmed by histopathological findings. FIELD STRENGTH/SEQUENCE: 3.0T magnetic resonance imaging (MRI) DWI with eight b-values ranging from 0 to 1000 s/mm(2) . ASSESSMENT: Molecular diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and apparent diffusion coefficient (ADC) were calculated by biexponential and monoexponential models fits, respectively. STATISTICAL TESTS: Comparisons were made between the MIBC and NMIBC group, and differences were analyzed by comparing the areas under the receiver-operating characteristic curves (AUCs). The correlations between these parameters and Ki-67 LI were assessed by Spearman's rank correlation analysis. RESULTS: The ADC and D value were significantly lower in patients with MIBC compared to those with NMIBC (P < 0.01). No significant (P > 0.05) differences were observed in D* and f. The AUC of D value (0.894) was significantly (P < 0.05) larger than the ADC value (0.786), with sensitivities and specificities of 95% and 87.5% (D) and 80% and 68.7% (ADC), respectively. In addition, the D and ADC values were significantly correlated with Ki-67 LI (r = -0.785, r = -0.643, respectively; both P < 0.01). DATA CONCLUSION: The D value obtained from IVIM exhibited better performance than conventional DWI for distinguishing NMIBC from MIBC and may serve as a potential imaging biomarker for bladder cancer invasion. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1054-1060.	bladder
Differential expression profile analysis of lncRNA UCA1α regulated mRNAs in bladder cancer.	Urothelial carcinoma associated 1α (UCA1α) is a novel long non-coding RNA (lncRNA) that regulates bladder cancer proliferation, migration, and invasion. The target genes of UCA1α have, however, not been identified. To address this, a pCDNA3.1(+)-UCA1α over-expression vector was transfected into UM-UC-2 bladder cancer cells. Genes differentially expressed between pCDNA3.1(+)-UCA1α and pCDNA3.1(+) transfected cell were then detected by microarray and bioinformatics analysis. A total of 71 differentially expressed genes were identified, including 52 up-regulated genes and 19 down-regulated genes. As expected, the lncRNA UCA1α expression level was significantly increased when compared to that of pCDNA3.1(+) transfected cells. The five most significantly up-regulated and five most significantly down-regulated genes were selected, and their expression levels were also assessed by real time quantitative polymerase chain reaction and Western blot. The mRNA and protein expression levels of FOXI3 and GSTA3 were found to be significantly increased, and those of MED18 and TEX101 were found to be significantly decreased. Gene ontology (GO) clustering identified several significant biological processes, cellular components, and molecular functions, associated with lncRNA UCA1α over-expression. The differentially expressed genes were involved in several significant pathways as shown by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway clustering. Cell proliferation activity was significantly increased following overexpression of lncRNA UCA1α increasing over culture time. The present study identifies, for the first time, potential target genes for lncRNA UCA1α in bladder cancer, and provides a significant reference for studying the role of lncRNA UCA1α in bladder cancer.	bladder
The Prolidase Activity, Oxidative Stress, and Nitric Oxide Levels of Bladder Tissues with or Without Tumor in Patients with Bladder Cancer.	This study was designed to evaluate the malondialdehyde (MDA), glutathione (GSH) and nitric oxide (NO) levels, and also prolidase, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) enzyme activities in malignant and benign cancers of bladder tissue. A total of 59 patients admitted to our clinic due to microscopic or macroscopic haematuria, were prospectively included in the study. Because of some reasons (no request to participate in the study, the inability to reach, other malignancies, alcohol consumption, metabolic disease), eight patients were excluded from study. Of the 51 patients, 25 were bladder tumor patients, and 26 were patients without cancers. The bladder tissue samples were obtained from all patients under anesthesia (spinal, epidural or general) for the measurement of MDA, GSH and NO levels, and prolidase, GSH-Px and SOD enzyme activities. Among the patients with bladder cancers, 7 patients were females and 18 patients were males, with an average age of 68.4 ± 2.49. Among patients without tumors, 6 patients were females and 20 patients were males, with an average age of 58 ± 2.05. In patients with bladder tumors, the oxidants (MDA, NO, prolidase) were higher, and the antioxidants (SOD, GSH, GSH-Px) were lower than those in patients without tumors. It was concluded that the oxygen free radicals play a role in the etiology of bladder cancers similar to many other tumors and inflammatory conditions. Therefore, we assume that antioxidants may provide benefits in the prevention and treatment of bladder cancer.	bladder
The Phosphatidylinositol 3-Kinase Pathway as a Potential Therapeutic Target in Bladder Cancer.	Purpose: Activation of the PI3K pathway occurs in over 40% of bladder urothelial cancers. The aim of this study is to determine the therapeutic potential, the underlying action, and the resistance mechanisms of drugs targeting the PI3K pathway.Experimental Design: Urothelial cancer cell lines and patient-derived xenografts (PDXs) were analyzed for alterations of the PI3K pathway and for their sensitivity to the small-molecule inhibitor pictilisib alone and in combination with cisplatin and/or gemcitabine. Potential predictive biomarkers for pictilisib were evaluated, and RNA sequencing was performed to explore drug resistance mechanisms.Results: The bladder cancer cell line TCCSUP, which harbors a PIK3CA E545K mutation, was sensitive to pictilisib compared to cell lines with wild-type PIK3CA Pictilisib exhibited stronger antitumor activity in bladder cancer PDX models with PI3KCA H1047R mutation or amplification than the control PDX model. Pictilisib synergized with cisplatin and/or gemcitabine in vitro, significantly delayed tumor growth, and prolonged survival compared with single-drug treatment in the PDX models. The phosphorylation of ribosomal protein S6 correlated with response to pictilisib both in vitro and in vivo, and could potentially serve as a biomarker to predict response to pictilisib. Pictilisib activated the compensatory MEK/ERK pathway that likely contributed to pictilisib resistance, which was reversed by cotreatment with the RAF inhibitor sorafenib. RNA sequencing of tumors resistant to treatment suggested that LSP1 downregulation correlated with drug resistance.Conclusions: These preclinical results provide new insights into the therapeutic potential of targeting the PI3K pathway for the treatment of bladder cancer. Clin Cancer Res; 23(21); 6580-91. ©2017 AACR.	bladder
Prognostic Value of TERT Alterations, Mutational and Copy Number Alterations Burden in Urothelial Carcinoma.	Point mutations in the TERT gene promoter occur at high frequency in multiple cancers, including urothelial carcinoma (UC). However, the relationship between TERT promoter mutations and UC patient outcomes is unclear due to conflicting reports in the literature. In this study, we examined the association of TERT alterations, tumor mutational burden per megabase (Mb), and copy number alteration (CNA) burden with clinical parameters and their prognostic value in a cohort of 398 urothelial tumors. The majority of TERT mutations were located at two promoter region hotspots (chromosome 5, 1 295 228 C>T and 1 295 250 C>T). TERT alterations were more frequently present in bladder tumors than in upper tract tumors (73% vs 53%; p=0.001). ARID1A, PIK3CA, RB1, ERCC2, ERBB2, TSC1, CDKN1A, CDKN2A, CDKN2B, and PTPRD alterations showed significant co-occurrence with TERT alterations (all p<0.0025). TERT alterations and the mutational burden/Mb were independently associated with overall survival (hazard ratio[HR] 2.31, 95% confidence interval [CI] 1.46-3.65; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), disease-specific survival (HR 2.23, 95% CI 1.41-3.53; p<0.001; and HR 0.96, 95% CI 0.93-0.99; p=0.002), and metastasis-free survival (HR 1.63, 95% CI 1.05-2.53; p=0.029; and HR 0.98, 95% CI 0.96-1.00; p=0.063) in multivariate models. PATIENT SUMMARY: The majority of TERT gene mutations that we detected in urothelial carcinoma are located at two promoter hotspots. Urothelial tumors with TERT alterations had worse prognosis compared to tumors without TERT alterations, whereas tumors with a higher mutational burden had more favorable outcome compared to tumors with low mutational burden.	bladder
Primary malignant mesenchymoma of bladder: Case report and review of the literature.	RATIONALE: Malignant mesenchymoma (MM) is defined as a heterogeneous malignant soft tissue tumor that consists of 2 or more distinctly different mesenchymal components in addition to fibrosarcomatous elements. Bladder MM was rarely reported in the literature and there are only 5 cases of primary bladder MM documented in English literature to date. PATIENT CONCERNS: A 58-year-old male complained of difficulty in urination and intermittent gross hematuria for 3 months. Doppler ultrasound scan revealed an avascular and homogeneous hypoechoic mass measured 6.5 × 9 cm in the bladder. Computed tomography showed a homogeneous solid mass in the bladder. DIAGNOSES: Pathology revealed spindle-shaped tumor and proliferation of poorly differentiated immature mesenchymal cells rich in eosinophilic cytoplasm with hyperchromatic sticklike nuclei. Immunohistochemical examinations were positive for CD117. INTERVENTIONS: The patient was diagnosed with presence of bladder tumor and underwent radical cystectomy; the optimal treatment strategy was reviewed and discussed. OUTCOMES: There was no recurrence or metastasis during a 16-month follow-up. LESSONS: Our case study demonstrated bladder MM with a relatively indolent clinical course. A multidisciplinary approach including surgery, radiotherapy, and chemotherapy may be useful. Radical resection is the most important determinant of clinical outcome. Generally, the clinical outcome and prognosis of mesenchymoma are favorable.	bladder
"Commentary on: ""Comprehensive transcriptional analysis of early-stage urothelial carcinoma."" Hedegaard J, Lamy P, Nordentoft I, Algaba F, Høyer S, Ulhøi BP, Vang S, Reinert T, Hermann GG, Mogensen K, Thomsen MB, Nielsen MM, Marquez M, Segersten U, Aine M, Höglund M, Birkenkamp-Demtröder K, Fristrup N, Borre M, Hartmann A, Stöhr R, Wach S, Keck B, Seitz AK, Nawroth R, Maurer T, Tulic C, Simic T, Junker K, Horstmann M, Harving N, Petersen AC, Calle ML, Steyerberg EW, Beukers W, van Kessel KE, Jensen JB, Pedersen JS, Malmström PU, Malats N, Real FX, Zwarthoff EC, Ørntoft TF, Dyrskjøt L. Cancer Cell. 2016 Jul 11;30(1):27-42."	Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into 3 major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed. Analysis of transcript variants revealed frequent mutations in genes encoding proteins involved in chromatin organization and cytoskeletal functions. Furthermore, mutations in well-known cancer driver genes (e.g., TP53 and ERBB2) were primarily found in high-risk tumors, together with APOBEC-related mutational signatures. The identification of subclasses in NMIBC may offer better prognostication and treatment selection based on subclass assignment.	bladder
Urinary bladder cancer staging in CT urography using machine learning.	PURPOSE: To evaluate the feasibility of using an objective computer-aided system to assess bladder cancer stage in CT Urography (CTU). MATERIALS AND METHODS: A dataset consisting of 84 bladder cancer lesions from 76 CTU cases was used to develop the computerized system for bladder cancer staging based on machine learning approaches. The cases were grouped into two classes based on pathological stage ≥ T2 or below T2, which is the decision threshold for neoadjuvant chemotherapy treatment clinically. There were 43 cancers below stage T2 and 41 cancers at stage T2 or above. All 84 lesions were automatically segmented using our previously developed auto-initialized cascaded level sets (AI-CALS) method. Morphological and texture features were extracted. The features were divided into subspaces of morphological features only, texture features only, and a combined set of both morphological and texture features. The dataset was split into Set 1 and Set 2 for two-fold cross-validation. Stepwise feature selection was used to select the most effective features. A linear discriminant analysis (LDA), a neural network (NN), a support vector machine (SVM), and a random forest (RAF) classifier were used to combine the features into a single score. The classification accuracy of the four classifiers was compared using the area under the receiver operating characteristic (ROC) curve (A(z) ). RESULTS: Based on the texture features only, the LDA classifier achieved a test A(z) of 0.91 on Set 1 and a test A(z) of 0.88 on Set 2. The test A(z) of the NN classifier for Set 1 and Set 2 were 0.89 and 0.92, respectively. The SVM classifier achieved test A(z) of 0.91 on Set 1 and test A(z) of 0.89 on Set 2. The test A(z) of the RAF classifier for Set 1 and Set 2 was 0.89 and 0.97, respectively. The morphological features alone, the texture features alone, and the combined feature set achieved comparable classification performance. CONCLUSION: The predictive model developed in this study shows promise as a classification tool for stratifying bladder cancer into two staging categories: greater than or equal to stage T2 and below stage T2.	bladder